Portal vein thrombosis in hepatocellular carcinoma: age and sex distribution in an autopsy study.

The purpose of this work was to investigate the prevalence, associated features and effect on survival of portal vein thrombosis (PVT) complicating hepatocellular carcinoma (HCC). The autopsy data of a series of 72 consecutive patients (57 male, 15 female) with HCC were reviewed. PVT was found in 32/72 patients (44%), and tended to be more common in female patients (10/15 versus 22/57, P = 0.052). Stratifying the data according to gender, it appeared that the mean age of patients with PVT compared to those without was greater in woman (71.9 +/- 5.9 versus 63.2 +/- 6.9 years, P = 0.024) and younger in men (58.8 +/- 8.9 versus 66.0 +/- 9.9 years, P = 0.007). When PVT was present, it was more likely that a definite diagnosis of HCC had been obtained before autopsy (P = 0.0001) and that death had been caused by bleeding complications (P = 0.007). Median survival times were similar, irrespective of the presence of PVT. During the natural history of HCC, PVT occurs in a substantial proportion of patients. Hormonal factors may have a permissive role in thrombus formation or neoplastic vascular invasion. Although in the presence of PVT a diagnosis of HCC is rarely missed and bleeding complications are likely to occur, patient survival does not seem to be significantly affected.

DNA index shift with disease progression in colorectal adenocarcinoma: a morphological and flow cytometric study.

DNA index (DI) values seen in 86 sporadic colorectal adenocarcinomas were related to clinical, morphological, and disease progression features. DI, whose overall distribution was bimodal with peaks in the diploid and from hypotriploid to tetraploid ranges, was related to pathological lymph node staging (pN), staging, lymphoid reaction, and tubular configuration. With increasing severity in pathological features, an irregular shift in DI class prevalence was seen, with no steady increase from diploidy to higher degrees of aneuploidy. All UICC stage I tumors (13% of total) were aneuploid, 50% being hypertriploid; diploidy (35%) and hypertriploidy (22%) prevailed in stage II carcinomas (41% of total), diploidy (35%) and hypotriploidy (30%) in stage III (30% of total), and triploidy (33%) in stage IV (15% of total). Amongst features related to stage (lymphoid reaction, depth of neoplastic embolization, grading, tubular configuration, and polymorphism), few were associated with DI, and none influenced DI shift and class prevalence through the stages. The biological capabilities of colorectal adenocarcinoma in relation to stage are expressed by certain aneuploid DI classes (hypertriploidy: absence of extracolonic spread; hypotriploidy: lymph node metastases; triploidy: distant metastases). Diploidy is unrelated to criteria defining stage above I and predicts 50% of cases with development of metachronous metastases. Irregular DI class shift through the stages may be attributable to different pathways of cancerogenesis and disease progression in diploid versus aneuploid carcinomas. Alternatively, assuming that the diploid fraction in aneuploid tumors contains neoplastic cells, pure diploid carcinomas represent the selection of a vital clone that may give rise to a further mixed population whose aneuploid DI is different and best fitted to express the biological capabilities of that given stage.

High prevalence of infection with hepatitis G virus in patients with hepatic and extrahepatic malignancies.

BACKGROUND/AIMS: The pathogenic role of hepatitis G virus, the recently discovered blood-borne agent, is controversial. Our aim was to ascertain the prevalence of hepatitis G virus infection in hepatic and in extrahepatic malignancies. METHODS: We studied 166 Italian patients (112 male, 54 female, mean age 61.8+/-9.3, mean+/-SD, range 34-85). One hundred and eighteen had cirrhosis, which was complicated by hepatocellular carcinoma in 66 cases. Forty-eight patients had extra-hepatic malignancies. Circulating HGV RNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) of both the nonstructural-3 and 5'noncoding regions of the hepatitis G virus genome. Antibodies to the E2 protein of hepatitis G virus were detected by means of an enzyme-linked immunosorbent assay. RESULTS: Ongoing HGV infection was detected in 30/66 (46%) patients with hepatocellular carcinoma, 12/52 (23%) patients with cirrhosis, and 14/48 (29%) patients with extrahepatic malignancies (p<0.05). Evidence of exposure to hepatitis G virus (detection of either HGV RNA or anti-E2 antibodies) was found in 46% of patients with cirrhosis, 66% of patients with hepatocellular carcinoma, and 39% of patients with extrahepatic malignancies. Serum HGV RNA positivity was associated with a hematocrit value < or = 0.35 and with history of exposure to blood products (p<0.005). CONCLUSIONS: Ongoing hepatitis G virus infection is detected at a very high rate in patients with hepatocellular carcinoma, but is also fairly common in extrahepatic malignancies. Hepatitis G virus infection in these patients is likely to originate from exposure to blood products, and to persist because of deficient immune surveillance.

Chronic lymphocytic sialoadenitis in HCV-related chronic liver disease: comparison of Sjögren's syndrome.

With the aim of morphologically characterizing chronic sialoadenitis in patients with hepatitis C virus (HCV) chronic liver disease, labial salivary gland biopsies from 22 chronic HCV liver disease and from 10 primary Sjögren's syndrome patients were compared. Only focus score (number of aggregates with more than 50 lymphocytes per 4 mm2 of glandular tissue) and grading of inflammation were able to discriminate significantly between the two patient groups. Duct ectasia, acinar depletion, presence of lymphoid aggregates with less than 50 lymphocytes and of lymphoid infiltration within intralobular salivary duct epithelium were evident in both disease groups and appeared to be non-specific, mostly age-related changes. In both patient groups plasma cell and lymphocyte typing showed similar features: T-lymphocytes represented most of the lymphoid population, B lymphocytes were few unless follicles were present. Higher focus score values were associated with a plasma cell switch from an IgA to an IgM and/or IgG predominance. A greater morphological similarity was seen between biopsies of the primary Sjögren's syndrome group and those of female rather than male chronic HCV liver disease patients. Salivary gland tissue in HCV patients responds to damage in a fashion similar to primary Sjögren's syndrome, the only difference being a lesser degree of inflammation.

Increased soluble ICAM-1 concentration and impaired delayed-type hypersensitivity skin tests in patients with chronic liver disease.

AIMS/BACKGROUND: Soluble ICAM-1 may act as an antagonist of the membrane bound form, which is essential for the adhesion of leucocytes to endothelial cells. The aim of this study was to investigate whether the presence of high concentrations of soluble ICAM-1 are related to the impairment of delayed-type hypersensitivity reactions. METHODS: The study population comprised 73 patients (53 men and 20 women) with chronic liver disease (19 with chronic hepatitis, 36 with cirrhosis and 18 with hepatocellular carcinoma), and 21 age-matched controls (11 men and 10 women). Serum soluble ICAM-1 was measured using an enzyme immunoassay. Skin tests for seven different antigens (tetanus, diphtheria, streptococcus group C, tuberculin, Candida, tricophyton, and proteus) were considered positive when diameters > or = 2 mm were recorded; the diameters of positive tests were added to calculate a cumulative score. RESULTS: Patients with chronic liver disease had fewer positive skin tests (median 2) and a lower cumulative score (median 7) than controls (median 3 and 12, respectively). Multivariate analysis suggested the existence of an independent association between alkaline phosphatase and anergy to skin tests and between soluble ICAM-1 concentrations and the cumulative score. CONCLUSIONS: The strong association observed between increased soluble ICAM-1 concentrations and impairment of delayed-type hypersensitivity skin tests suggests that soluble ICAM-1 may be implicated in the immune depression seen in patients with chronic liver disease.

Non-small cell lung cancer. Morphology and DNA flow cytometry.

OBJECTIVE: To correlate stage-related and histologic features of non-small cell lung cancer (NSCLC) with DNA flow cytometric parameters. STUDY DESIGN: The clinicopathologic features, DNA flow cytometric parameters (ploidy type, S-phase fraction and DNA index [DI]) of 72 surgically resected NSCLC were reviewed. RESULTS: NSCLC were classified on the basis of their DI in diploid, peridiploid, hypotriploid, triploid, hypertriploid, tetraploid, hypertetraploid and multiploid tumors. DI was significantly related to pleural infiltration, pT, histologic type and evidence of necrosis. Tumors infiltrating the pleura were mostly triploid or hypertriploid; high pT stages were also hypertetraploid. Adenocarcinomas showed a wide DI distribution, squamous carcinomas were mostly diploid, triploid or hypertriploid and large cell carcinomas were mostly triploid, hypertriploid and hypertetraploid. The best combination of features able to predict disease relapse was pT plus pN plus grading and divergent differentiation. CONCLUSION: Many stage-related and histologic features are associated with particular DI classes, which vary in relation to the feature itself and, in some cases, regardless of classical methods of grading and histologic typing. DNA content analysis highlights greater biologic heterogeneity in NSCLC than evidenced morphologically.

DNA flow cytometry and glial fibrillary acidic protein reactivity in pleomorphic adenomas of the salivary glands.

OBJECTIVE: To evaluate and correlate morphologic features, glial fibrillary acidic protein (GFAP) reactivity and DNA content parameters in 32 pleomorphic adenomas of the salivary glands. STUDY DESIGN: The adenomas were subclassified according to the proportion of stroma and type of stromal differentiation. DNA flow cytometry was carried out on paraffin-embedded material. GFAP reactivity was determined immunohistochemically and evaluated as the percentage of positive cells. Follow-up ranged from 17 to 71 months; no recurrences were observed. RESULTS: Seven cases were aneuploid, 10 peridiploid and 15 diploid. Nondiploid tumors had a significantly higher S-phase fraction. Nondiploid adenomas were significantly associated with a greater percentage of stroma, while S-phase fraction showed only a trend toward being higher in tumors with a greater quota of stroma. Ploidy type and S-phase fraction were unrelated to sex, age, tumor diameter or site. GFAP reactivity was unrelated to subtype or S-phase fraction; a higher frequency of diploid tumors was seen among cases with a greater number of reactive cells. CONCLUSION: Aneuploidy is present in a significant percentage of typical cases. It is unrelated to tumor bulk and appears to have no effect on recurrence as long as surgical excision is complete.